tbuckley/cabot-search huggingface dataset:
A myogenic niche with a proper mechanical stress environment improves abdominal wall muscle repair by modulating immunity and preventing fibrosis
Authors: Shengyu Wang, Huige Yan, Bin Fang, Chenhui Gu, Jiandong Guo, Pengchen Qiu, Nan Song, Wenbing Xu, Jianfeng Zhang, Xianfeng Lin, Xiangqian Fang
Journal: Biomaterials (2022)
Myocardial Contractile Mechanics in Ischemic Mitral Regurgitation
Authors: Jonathan D. Kochav, Jiwon Kim, Robert Judd, Katherine A. Tak, Emmad Janjua, Abigail J. Maciejewski, Han W. Kim, Igor Klem, John Heitner, Dipan Shah, William A. Zoghbi, Chetan Shenoy, Afshin Farzaneh-Far, Venkateshwar Polsani, Pablo Villar-Calle, Michele Parker, Kevin M. Judd, Omar K. Khalique, Martin B. Leon, Richard B. Devereux, Robert A. Levine, Raymond J. Kim, Jonathan W. Weinsaft
Journal: JACC. Cardiovascular imaging (2022)
A risk model for digital breast tomosynthesis to predict breast cancer and guide clinical care
Authors: Mikael Eriksson, Stamatia Destounis, Kamila Czene, Andrew Zeiberg, Robert Day, Emily F. Conant, Kathy Schilling, Per Hall
Journal: Science Translational Medicine (2022)

Screening with digital breast tomosynthesis (DBT) improves breast cancer detection and reduces false positives. However, currently, no breast cancer risk model takes advantage of the additional information generated by DBT imaging for breast cancer risk prediction. We developed and internally validated a DBT-based short-term risk model for predicting future late-stage and interval breast cancers after negative screening exams. We included the available 805 incident breast cancers and a random sample of 5173 healthy women matched on year of study entry in a nested case-control study from 154,200 multiethnic women, aged 35 to 74, attending DBT screening in the United States between 2014 and 2019. A relative risk model was trained using elastic net logistic regression and nested cross-validation to estimate risks for using imaging features and age. An absolute risk model was developed using derived risks and U.S. incidence and competing mortality rates. Absolute risks, discrimination performance, and risk stratification were estimated in the left-out validation set. The discrimination performance of 1-year risk was 0.82 (95% CI, 0.79 to 0.85) with good calibration ( P = 0.7). Using the U.S. Preventive Service Task Force guidelines, 14% of the women were at high risk, 19.6 times higher compared to general risk. In this high-risk group, 76% of stage II and III cancers and 59% of stage 0 cancers were observed ( P &lt; 0.01). Using mammographic features generated from DBT screens, our image-based risk prediction model could guide radiologists in selecting women for clinical care, potentially leading to earlier detection and improved prognoses.
Long‐term outcomes of patients with conjunctival extranodal marginal zone lymphoma
Authors: Eduardo Edelman Saul, Juan Pablo Alderuccio, Isildinha M. Reis, Wei Zhao, Sunil G. Iyer, Gregor Rodriguez, Amrita Desai, Jennifer R. Chapman, David T. Tse, Arnold M. Markoe, Derek M. Isrow, Izidore S. Lossos
Journal: American Journal of Hematology (2022)

Comprehensive information on clinical features and long-term outcomes of primary conjunctival extranodal marginal zone lymphoma (PCEMZL) is scarce. We present a large single-institution retrospective study of 72 patients. The median age was 64 years, and 63.9% were female. Stage I was present in 87.5%. Radiation therapy (RT) alone was the most common treatment (70.8%). Complete response (CR) was 87.5%, and 100% in RT-treated patients. With a median follow-up of 6.7 years, relapse/progression and death occurred in 19.4% each, with one relapse within the RT field. The 10-year progression-free survival (PFS) and overall survival (OS) were 68.4% (95% CI 52.8%-79.8%) and 89.4% (95% CI 77.4%-95.2%), respectively. The 10-year rate for time to progression from diagnosis was 22.5% (95% CI 11.6%-35.7%). The 10-year PFS and OS of MALT-IPI 0 versus 1-2 were 83.3% versus 51.3%, (p = .022) and 97.6% versus 76.6%, (p = .0052), respectively. The following characteristics were associated with shorter survival: age > 60 years (PFS: HR = 2.93, 95% CI 1.08-7.95; p = .035, OS: HR = 9.07, 95% CI 1.17-70.26; p = .035) and MALT-IPI 1-2 (PFS: HR = 2.67, 95% CI 1.12-6.31; p = .027, OS: HR = 6.64, 95% CI 1.45-30.37; p = .015). CR following frontline therapy was associated with longer PFS (HR = 0.13, 95% CI 0.04-0.45; p = .001), but not OS. Using the Fine and Gray regression model with death without relapse/progression as a competing risk, RT and CR after frontline therapy were associated with lower risk of relapse (SHR = 0.34, 95% CI 0.12-0.96 p = .041 and SHR = 0.11, 95% CI 0.03-0.36; p < .001, respectively). Patients with PCEMZL treated with frontline RT exhibit excellent long-term survival, and the MALT-IPI score appropriately identifies patients at risk for treatment failure.
Clinical, Brain, and Multilevel Clustering in Early Psychosis and Affective Stages
Authors: Dominic B. Dwyer, Madalina-Octavia Buciuman, Anne Ruef, Joseph Kambeitz, Mark Sen Dong, Caedyn Stinson, Lana Kambeitz-Ilankovic, Franziska Degenhardt, Rachele Sanfelici, Linda A. Antonucci, Paris Alexandros Lalousis, Julian Wenzel, Maria Fernanda Urquijo-Castro, David Popovic, Oemer Faruk Oeztuerk, Shalaila S. Haas, Johanna Weiske, Daniel Hauke, Susanne Neufang, Christian Schmidt-Kraepelin, Stephan Ruhrmann, Nora Penzel, Theresa Lichtenstein, Marlene Rosen, Katharine Chisholm, Anita Riecher-Rössler, Laura Egloff, André Schmidt, Christina Andreou, Jarmo Hietala, Timo Schirmer, Georg Romer, Chantal Michel, Wulf Rössler, Carlo Maj, Oleg Borisov, Peter M. Krawitz, Peter Falkai, Christos Pantelis, Rebekka Lencer, Alessandro Bertolino, Stefan Borgwardt, Markus Noethen, Paolo Brambilla, Frauke Schultze-Lutter, Eva Meisenzahl, Stephen J. Wood, Christos Davatzikos, Rachel Upthegrove, Raimo K. R. Salokangas, Nikolaos Koutsouleris, Amatya Mackintosh, Nathalie Kaiser, Thorsten Lichtenstein, Mauro Seves, Katie Chisholm, Renate Reniers, Alexandra Stainton, Tiina From, Markus Heinimaa, Tuula Ilonen, Päivi Jalo, Heikki Laurikainen, Lauri Tuominen, Sinikka Luutonen, Janina Paju, Maria Tikka, Reetta-Liina Armio (Säilä), Anna Toivonen, Maija Walta, Franco Fabbro, Matteo Balestrieri, Carolina Bonivento, Marco Garzitto, Giuseppe Cabras, Sara Piccin, Umberto Castellani, Marcella Bellani, Marta Maieron, Rossano Girometti, Chiara Zuiani, Stan Skafidas, Dennis Velakoulis, Ian Everall, Antonia Merritt, Michael Jovicevic, Manuel Plicht, Dirk Bequé, Ana Beatriz Solana Sánchez, Nicolas Hehn, Katrin Herrmann, Michael X. Burke, Brice Fernandez, Carlo Altamura, Mario Rango, Adele Ferro, Marika Belleri, Eleonora Maggioni, Letizia Squarcina, Marta Re, Giuseppe Delvecchio, Anna Meneghelli, Emiliano Monzani, Roberto Sassi, Maurizio Sberna, Luciana Gennari, Patrizia Torremante, Marian Surmann, Udo Dannlowski, Olga Bienek, Giuseppe Blasi, Giulio Pergola, Tiziana Quarto, Ileana Andriola, Raffaella Romano, Barbara Gelao, Leonardo Fazio, Alexandra Korda, Henrik Rohner, Matthias Mann, Phillip Geyer, Peter Treit, Johannes Müller, Richard Frackowiak, Danuta Wasserman, Wolfgang Maier, Elisabeth Binder, Christiane Woopen, Tade Matthias Spranger, Karl-Heinz Möhrmann
Journal: JAMA Psychiatry (2022)

Approaches are needed to stratify individuals in early psychosis stages beyond positive symptom severity to investigate specificity related to affective and normative variation and to validate solutions with premorbid, longitudinal, and genetic risk measures.
Abstract A016: Mapping of subclonal events in multi-region multi-omics oncogenomics studies
Authors: Mark Tran, Nicholas McGranahan, Chris Barnes, Javier Herrero
Journal: Cancer Research (2022)

Abstract Advanced cancer genomics relies on multi-region sequencing to detect intra-tumor heterogeneity. These data allow for backtracking tumor’s evolutionary history by inferring its clonal population structure (Roth et al. 2014) and reconstructing a phylogenetic tree (Malikic et al. 2015). However, methods for mapping subclonal copy number changes onto tumor evolutionary trees are still lacking. McGranahan et al. 2017 presented LOHHLA, a tool for estimation of allele-specific HLA loss from sequencing data, which demonstrated the effects of loss of heterozygosity of HLA on early-stage non-small-cell lung cancer. Here, we present MAPping SubClonal Events (MAPSCE), a tool for mapping subclonal copy number events on the tumor evolutionary trees. Similar to LOHHLA, MAPSCE uses Quadratic Programming for the branch test, where copy-number states before and after a branch are estimated, one branch at a time. Additionally, it relies on the Bayesian Information Criterion from bootstrapped samples to compare the results for each branch and the null hypothesis (H0 = no subclonal event). While mapping loss of heterozygosity events of HLA allele in TRACERx 100 cohort (Jamal-Hanjani et al. 2017) MAPSCE pre-empts the need for manual review on LOHHLA’s initial results, can take into account multiple possible solutions and maintains high accuracy of the results. Using simulated data sets we tested the robustness of MAPSCE to the addition of noise to the cluster CCFs that define each tumor clone. MAPSCE outperforms LOHHLA’s mapping of subclonal LOH events when adding noise up to ±25% CCF. Sub-clonal LOH affecting larger clones are easier to detect and both LOHHLA and MAPSCE produce similar results. However, only MAPSCE maintains high accuracy in detecting events affection smaller clones. In data sets with simulated amplification and duplication events, MAPSCE can also identify duplication and amplification events with at least 70% accuracy up to ±20% CCF noise range. In the future, we are planning to extend this approach to other data types such as gene expression and methylation data, a combination of which would allow us to identify the biological events underlying the formation of new tumor clones, to ultimately integrate these in a comprehensive model of cancer evolution. Citation Format: Mark Tran, Nicholas McGranahan, Chris Barnes, Javier Herrero. Mapping of subclonal events in multi-region multi-omics oncogenomics studies [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A016.
Pyruvate Kinase M1 Suppresses Development and Progression of Prostate Adenocarcinoma
Authors: Shawn M. Davidson, Daniel R. Schmidt, Julia E. Heyman, James P. O'Brien, Amy C. Liu, William J. Israelsen, Talya L. Dayton, Raghav Sehgal, Roderick T. Bronson, Elizaveta Freinkman, Howard H. Mak, Giuseppe Nicolò Fanelli, Scott Malstrom, Gary Bellinger, Arkaitz Carracedo, Pier Paolo Pandolfi, Kevin D. Courtney, Abhishek Jha, Ronald A. DePinho, James W. Horner, Craig J. Thomas, Lewis C. Cantley, Massimo Loda, Matthew G. Vander Heiden
Journal: Cancer Research (2022)

Abstract Altered metabolism helps sustain cancer cell proliferation and survival. Most cancers, including prostate cancers, express the M2 splice isoform of pyruvate kinase (PKM2), which can support anabolic metabolism to support cell proliferation. However, Pkm2 expression is dispensable for the formation and growth of many cancers in vivo. Expression of pyruvate kinase isoform M1 (Pkm1) is restricted to relatively few tissues and has been reported to promote growth of select tumors, but the role of PKM1 in cancer has been less studied than PKM2. To test how differential expression of pyruvate kinase isoforms affects cancer initiation and progression, we generated mice harboring a conditional allele of Pkm1 and crossed these mice, or those with a Pkm2 conditional allele, with a Pten loss-driven prostate cancer model. Pkm1 loss led to increased PKM2 expression and accelerated prostate cancer development, whereas Pkm2 deletion led to increased PKM1 expression and suppressed tumor progression. Metabolic profiling revealed altered nucleotide levels in tumors with high PKM1 expression, and failure of these tumors to progress was associated with DNA replication stress and senescence. Consistent with these data, a small molecule pyruvate kinase activator that mimics a high activity PKM1-like state suppressed progression of established prostate tumors. Analysis of human specimens showed PKM2 expression is retained in most human prostate cancers. Overall, this study uncovers a role for pyruvate kinase isoforms in prostate cancer initiation and progression, and argues that pharmacologic pyruvate kinase activation may be beneficial for treating prostate cancer. Significance: Differential expression of PKM1 and PKM2 impacts prostate tumorigenesis and suggests a potential therapeutic vulnerability in prostate cancer.
Phase II Clinical Trial of Eribulin–Gemcitabine Combination Therapy in Previously Treated Patients With Advanced Liposarcoma or Leiomyosarcoma
Authors: Chang Gon Kim, Nam Suk Sim, Jeong Eun Kim, Kum-Hee Yun, Young Han Lee, Seung Hyun Kim, Wooyeol Baek, Yoon Dae Han, Sang Kyum Kim, Jee Hung Kim, Yoon Woo Koh, Inkyung Jung, Su-Jin Shin, Sun Young Rha, Jin-Hee Ahn, Hyo Song Kim
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Monotherapy with eribulin or gemcitabine has been found to be moderately effective in treating soft-tissue sarcomas (STS). In this study, we evaluated the efficacy and safety of eribulin–gemcitabine combination therapy for the two most common histologic types of STS, liposarcoma and leiomyosarcoma. Patients and Methods: In this nonrandomized, multicenter, phase II study, we included patients with progressive disease who had received one or two courses of chemotherapy that included doxorubicin. Patients were administered 1.4 mg/m2 eribulin and 1,000 mg/m2 gemcitabine on days 1 and 8 every 3 weeks. The primary endpoint was progression-free survival rate at 12 weeks (PFSR12wks), with null and alternative hypotheses of PFSR12wks ≤20.0% and ≥40.0%, respectively. Exploratory biomarker analyses with next-generation sequencing (NGS) were performed on pretreatment tumor samples. Results: Among the 37 patients included, the overall PFSR12wks was 73.0%, achieving the primary endpoint. The objective response rate, disease control rate, median progression-free survival, and median overall survival were 16.2%, 78.4%, 5.6 months, and 31.9 months, respectively, without differences according to histologic type. New safety signals and treatment-related deaths were not documented. NGS-based transcriptome analysis revealed that functional enrichment in the TGFβ pathway was mostly associated with a poor outcome, whereas single genetic alterations largely failed to predict treatment outcome. Conclusions: Eribulin–gemcitabine combination therapy showed promising activity and an acceptable safety profile in patients with liposarcoma or leiomyosarcoma. Gene expression profiling with pathway enrichment analysis would have possibilities to have predictive value for survival outcome, necessitating further investigation to confirm.
Epistasis Creates Invariant Sites and Modulates the Rate of Molecular Evolution
Authors: Ravi Patel, Vincenzo Carnevale, Sudhir Kumar
Journal: Molecular Biology and Evolution (2022)

Abstract Invariant sites are a common feature of amino acid sequence evolution. The presence of invariant sites is frequently attributed to the need to preserve function through site-specific conservation of amino acid residues. Amino acid substitution models without a provision for invariant sites often fit the data significantly worse than those that allow for an excess of invariant sites beyond those predicted by models that only incorporate rate variation among sites (e.g., a Gamma distribution). An alternative is epistasis between sites to preserve residue interactions that can create invariant sites. Through computer-simulated sequence evolution, we evaluated the relative effects of site-specific preferences and site-site couplings in the generation of invariant sites and the modulation of the rate of molecular evolution. In an analysis of ten major families of protein domains with diverse sequence and functional properties, we find that the negative selection imposed by epistasis creates many more invariant sites than site-specific residue preferences alone. Further, epistasis plays an increasingly larger role in creating invariant sites over longer evolutionary periods. Epistasis also dictates rates of domain evolution over time by exerting significant additional purifying selection to preserve site couplings. These patterns illuminate the mechanistic role of epistasis in the processes underlying observed site invariance and evolutionary rates.
Socioeconomic status associates with worse asthma morbidity among Black and Latinx adults
Authors: Juan Carlos Cardet, Ku-Lang Chang, Benjamin J Rooks, Jennifer K Carroll, Juan Carlos Celedón, Tamera Coyne-Beasley, Jing Cui, Brianna Ericson, Victoria E Forth, Maureen Fagan, Anne L Fuhlbrigge, Paulina Arias Hernandez, Jean Kruse, Margee Louisias, Nancy E Maher, Brian Manning, Wilson D Pace, Wanda Phipatanakul, Jacqueline Rodriguez-Louis, Joel B Shields, Elliot Israel, Juan P Wisnivesky
Journal: Journal of Allergy and Clinical Immunology (2022)
Asclepius Revisited—Ancient Myth and 21st-Century Psychedelic Medicine
Authors: Richard R. Szuster
Journal: JAMA (2022)

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Robust hydrogel adhesives for emergency rescue and gastric perforation repair
Authors: Jing Yu, Yanyang Qin, Yuxuan Yang, Xiaodan Zhao, Zixi Zhang, Qiang Zhang, Yaqiong Su, Yanfeng Zhang, Yilong Cheng
Journal: Bioactive Materials (2022)

Development of biocompatible hydrogel adhesives with robust tissue adhesion to realize instant hemorrhage control and injury sealing, especially for emergency rescue and tissue repair, is still challenging. Herein, we report a potent hydrogel adhesive by free radical polymerization of N-acryloyl aspartic acid (AASP) in a facile and straightforward way. Through delicate adjustment of steric hindrance, the synergistic effect between interface interactions and cohesion energy can be achieved in PAASP hydrogel verified by X-ray photoelectron spectroscopy (XPS) analysis and simulation calculation compared to poly (N-acryloyl glutamic acid) (PAGLU) and poly (N-acryloyl amidomalonic acid) (PAAMI) hydrogels. The adhesion strength of the PAASP hydrogel could reach 120 kPa to firmly seal the broken organs to withstand the external force with persistent stability under physiological conditions, and rapid hemostasis in different hemorrhage models on mice is achieved using PAASP hydrogel as physical barrier. Furthermore, the paper-based Fe3+ transfer printing method is applied to construct PAASP-based Janus hydrogel patch with both adhesive and non-adhesive surfaces, by which simultaneous wound healing and postoperative anti-adhesion can be realized in gastric perforation model on mice. This advanced hydrogel may show vast potential as bio-adhesives for emergency rescue and tissue/organ repair.
Modifiable Risk Factors for Alzheimer Disease and Related Dementias Among Adults Aged ≥45 Years — United States, 2019
Authors: John D. Omura, Lisa C. McGuire, Roshni Patel, Matthew Baumgart, Raza Lamb, Eva M. Jeffers, Benjamin S. Olivari, Janet B. Croft, Craig W. Thomas, Karen Hacker
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Alzheimer disease,* the most common cause of dementia, affects an estimated 6.5 million persons aged ≥65 years in the United States (1). A growing body of evidence has identified potential modifiable risk factors for Alzheimer disease and related dementias (ADRD) (1-3). In 2021, the National Plan to Address Alzheimer's Disease (National Plan) introduced a new goal to "accelerate action to promote healthy aging and reduce risk factors for Alzheimer's disease and related dementias" to help delay onset or slow the progression of ADRD (3). To assess the status of eight potential modifiable risk factors (i.e., high blood pressure, not meeting the aerobic physical activity guideline, obesity, diabetes, depression, current cigarette smoking, hearing loss, and binge drinking), investigators analyzed data from the cognitive decline module that was administered to adults aged ≥45 years in 31 states and the District of Columbia (DC)† in the 2019 Behavioral Risk Factor Surveillance System (BRFSS) survey. Among the risk factors, prevalence was highest for high blood pressure (49.9%) and lowest for binge drinking (10.3%) and varied by selected demographic characteristics. Adults with subjective cognitive decline (SCD),§ an early indicator of possible future ADRD (4), were more likely to report four or more risk factors than were those without SCD (34.3% versus 13.1%). Prevalence of SCD was 11.3% overall and increased from 3.9% among adults with no risk factors to 25.0% among those with four or more risk factors. Implementing evidence-based strategies to address modifiable risk factors can help achieve the National Plan's new goal to reduce risk for ADRD while promoting health aging.¶,*.
Advanced basal cell carcinoma: What dermatologists need to know about treatment
Authors: Melissa Wilson, Ryan P. Johnson, Stephen C. Senft, Eva Y. Pan, Andrew C. Krakowski
Journal: Journal of the American Academy of Dermatology (2022)

The treatment of advanced basal cell carcinoma (BCC) often requires therapies beyond local surgical excision or radiation due to the invasiveness of the tumor. Historically, cytotoxic chemotherapy was used to treat advanced BCC, but with limited data, no standard regimens were established. The discovery of cyclopamine, a natural inhibitor in the Hedgehog pathway, led to the development of the 2 currently approved Hedgehog inhibitors, vismodegib and sonidegib. Both agents are indicated for locally advanced BCC, while vismodegib is also indicated for metastatic BCC. In patients who progress on hedgehog inhibitors or cannot tolerate hedgehog inhibitors, the programmed cell death protein 1 inhibitor cemiplimab can be used to treat locally advanced or metastatic disease. Complex cases of locally advanced or metastatic BCC may be best discussed through a multidisciplinary approach in order to determine the optimal treatment approach for the individual patient.
Reforming Nursing Home Financing, Payment, and Oversight
Authors: Rachel M. Werner, R. Tamara Konetzka, David C. Grabowski, David G. Stevenson
Journal: New England Journal of Medicine (2022)

More than 30 years after the Nursing Home Reform Act, the United States still fails to protect nursing home residents and provide them with high-quality care. The Covid-19 pandemic's devastating effect on nursing homes reminds us that further reforms are sorely needed.